2020 Articles

ZFP281 recruits polycomb repressive complex 2 to restrict extraembryonic endoderm potential in safeguarding embryonic stem cell pluripotency

Huang, Xin; Bashkenova, Nazym; Yang, Jihong; Li, Dan; Wang, Jianlong

Dear Editor, Cell-fate decisions are governed by comprehensive gene-regulatory programs. During the preimplantation development, at least two waves of cell fate decisions are made while the cells gradually lose their totipotency (Schrode et al., 2013). The first decision involves the spatial separation of outer-residing trophectoderm (TE) cells from inner cell mass (ICM) in E3.5 mouse blastocyst. The second decision involves gene expression refinements and active cell sorting within the ICM that ultimately results in epiblast (EPI) cells, residing deep within the ICM, and the primitive endoderm (PrE) cells comprising a monolayer of blastocoel-facing cells at the surface of the ICM (Schrode et al., 2013). OCT4, SOX2, and NANOG are master transcription factors (TFs) essential for the formation and maintenance of the pluripotent ICM cells and their in vitro counterparts mouse embryonic stem cells (ESCs). On the other hand, GATA4, GATA6, and SOX17 are master TFs of the PrE cells and their in vitro counterparts extraembryonic endoderm stem cells (XENs). Only naïve ESCs are capable of deriving both primed epiblast stem cells (EpiSCs) and XEN cells in vitro (Cho et al., 2012). Primed EpiSCs cannot derive XEN-like cells, suggesting that ESCs and EpiSCs have different levels of developmental potential (Cho et al., 2012). Understanding the mechanism of pluripotent state transition in vitro provides insights into dynamic control of in vivo developmental transition of embryonic potency while simultaneously preparing for the transition to the somatic lineages.